Investigating The Role Of Innate Inflammatory Pathways During Infection With Murine Coronavirus

Multicellular organisms are constantly exposed to microorganisms, such as viruses and bacteria, many of which are infectious pathogens. The immune system evolved to provide protection against these organisms, and includes numerous components to defend against a diverse, rapidly evolving pool of pathogens. The immune system is classically divided into two arms, the innate and adaptive systems. The time and metabolic cost of activating the T and B cell responses are considerable, and can also have deleterious side effects if the response is not properly controlled. Therefore, the adaptive immune system is carefully regulated so as to be activated only when necessary. The innate immune system serves to control most pathogens in a more rapid, less energetically expensive manner than the adaptive immune system, and to help regulate subsequent immune responses, guiding and controlling them in order to most efficiently clear pathogens with a minimum of pathological side effects. Among the first elements of the innate system that pathogens encounter are pattern recognition receptors, invariant receptors that detect conserved pathogen associated molecular patterns. Upon recognizing its binding ligand, a pattern recognition receptor will activate a signaling cascade that often triggers production and/or release of one or more pro- inflammatory cytokines. These in turn modulate additional elements of both the innate and adaptive immune responses, and are often critical lynchpins of host defense. Due to this central role in the immune system we investigated the roles of two distinct innate inflammatory pathways, the inflammasome and the MDA5-dependent portion of the type 1 interferon response, during infection with the murine coronavirus mouse hepatitis virus (MHV). Utilizing transgenic mice deficient in Caspase-1 and -11, which catalyze all inflammasome processing, the IL-1 receptor, the IL-18 receptor, or MDA5, we characterize the disease course and subsequent immune response following infection with MHV, a model murine coronavirus. We find that inflammasome signaling is protective during infection, and that much or all of this protection is mediated by IL-18 signaling driving production of interferon gamma by T cells. We also demonstrate that MDA5 signaling controls viral tropism and replication, and that in its absence the host immune response becomes over active, likely leading to lethal pathology. Overall, our studies help define how innate inflammatory pathways can have diverse influences on pathogenesis and the immune response.

Overall recent research on TLRs has led to tremendous increase in our understanding of early steps in pathogen recognition and will presumably lead to potent TLR targeting therapeutics in the future. This book reviews and highlights our recent understanding on the function and ligands of TLRs as well as their role in autoimmunity, dendritic cell activation and target structures for therapeutic intervention.

This volume provides various techniques and methodologies currently used in the study of MERS-CoV. Chapters are divided into four parts detailing evolution and entry of MERS-coronavirus, genetic alteration and structural determination of MERS-coronavirus proteins, quantitation of virus and anti-viral factors, and mouse models for MERS -coronavirus. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, MERS Coronavirus: Methods and Protocols aims to ensure successful results in the further study of this vital field.

SARS was the ?rst new plague of the twenty-?rst century. Within months, it spread worldwide from its “birthplace” in Guangdong Province, China, affecting over 8,000 people in 25 countries and territories across ?ve continents. SARS exposed the vulnerability of our modern globalised world to the spread of a new emerging infection. SARS (or a similar new emerging disease) could neither have spread so rapidly nor had such a great global impact even 50 years ago, and arguably, it was itself a product of our global inter-connectedness. Increasing af?uence and a demand for wild-game as exotic food led to the development of large trade of live animal and game animal markets where many species of wild and domestic animals were co-housed, providing the ideal opportunities for inter-species tra- mission of viruses and other microbes. Once such a virus jumped species and attacked humans, the increased human mobility allowed the virus the opportunity for rapid spread. An infected patient from Guangdong who stayed for one day at a hotel in Hong Kong led to the transmission of the disease to 16 other guests who travelled on to seed outbreaks of the disease in Toronto, Singapore, and Vietnam, as well as within Hong Kong itself. The virus exploited the practices used in modern intensive care of patients with severe respiratory disease and the weakness in infection control practices within our health care systems to cause outbreaks within hospitals, further amplifying the spread of the disease. Health-care itself has become a two-edged sword.

Resumen: Offers an integrated view of principal aspects of immune response to all types of infectious agents. Deals with the immune system primarily as a host defense system. Various infectious agents and diseases are integrated under general topics rather than treated in separate chapters.

Immunoregulation is one of the areas which has witnessed the most explosive advances of immunology during the past decade. It is in this area that the current view of the immune system has arisen and developed. There is indeed little doubt that immune reactions are primarily determined by messages which are genera ted within the immune system and passed among different types of immunologie cells. This cell communication not only determines the type, intensity and duration of the response after perturbation of the immune system by exogenous antigens, but it is also essential for preventing autoimmune reactions and their clinical conse quences. In order to assure aperfect balance within the enormous com plexity of the immune system, it is not surprising that multiple self-regulatory mechanisms are organized at different levels, such as antibody feedback, idiotypic-anti-idiotypic responses, suppres sor and helper T cells, lymphokine signals and genetic require ments. A nu mb er of observations in recent years have, however, demonstrated that consistent contributions to the immunological homeostasis are given also by signals generated outside of the immune system, namely,in the central and autonomous nervous system as weIl as in the endocrine apparatus. Furthermore, the interactions between the immune system and the other body homestatic mechanisms seem to be bidirectional: if immunological cells may be targets of neuroendocrinological factors, immunological products seem in turn to contribute to the neuro endocrine homeostasis.

Increasing scientific evidence suggests that the majority of diseases including cancer are driven by oxidative stress and inflammation, attributed to environmental factors. These factors either drive genetic mutations or epigenetically modify expression of key regulatory genes. These changes can occur as early as gestational fetal development, and

The first International Conference on Oral Mucosal Immunity and Microbiome (OMIM) aimed to highlight cutting-edge basic and translational research from an oral immunological and microbiological perspective. Oral diseases with a microbial etiology are the most prevalent chronic diseases of humans. Whilst not life-threatening, they can significantly compromise quality of life, are associated with increased risk for certain systemic diseases, and pose heavy financial burdens to national health systems. Hence, periodontal and peri-implant diseases, dental caries, root canal infections and mucosal infections are significant global public health problems. In this book global experts summarize and discuss the latest progress made in oral mucosal immunity and the oral microbiome. Target audience is basic and/or translational researchers with expertise in host immunity and microbiome research, and interest in oral health and disease. This volume provides a much needed quantum leap in the field, by joining forces to address gaps at the oral mucosal immunity-microbiome cross-talk.

Persistent Viral Infections Edited by Rafi Ahmed Emory Vaccine Center, Atlanta, USA and Irvin S. Y. Chen UCLA School of Medicine, Los Angeles, USA During the past decade much of our attention has focused on diseases associated with viral persistence. Major breakthroughs in immunology, and the advent of molecular approaches to study pathogenesis have increased our understanding of the complex virus-host interactions that occur during viral persistence. Persistent Viral Infections focuses on: * The pathogenesis and immunology of chronic infections * Animal models that provide, or have the potential to provide, major insights This volume will be essential reading for virologists, immunologists, oncologists and neurologists.

This volume is based on the 10th International Nidovirus Symposium: Towards Control of SARS and other Nidovirus Diseases. The volume includes articles by all of the major contributors to this burgeoning area of research which summarize the work presented at the meeting. This represents the only comprehensive book to cover this field in the last five years.